Method for radiation sterilization of medical devices

ABSTRACT

Methods and systems for selection radiation exposure in sterilization of medical devices are disclosed.

CROSS-REFERENCE TO RELATED APPLICATION

This is a divisional of U.S. application Ser. No. 11/803,829 filed May15, 2007 which claims priority to U.S. provisional application No.60/810,300 filed Jun. 1, 2006.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to radiation sterilization.

2. Description of the State of the Art

This invention relates to radially expandable endoprostheses, which areadapted to be implanted in a bodily lumen. An “endoprosthesis”corresponds to an artificial device that is placed inside the body. A“lumen” refers to a cavity of a tubular organ such as a blood vessel.

A stent is an example of such an endoprosthesis. Stents are generallycylindrically shaped devices, which function to hold open and sometimesexpand a segment of a blood vessel or other anatomical lumen such asurinary tracts and bile ducts. Stents are often used in the treatment ofatherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of the diameter of a bodily passage ororifice. In such treatments, stents reinforce body vessels and preventrestenosis following angioplasty in the vascular system. “Restenosis”refers to the reoccurrence of stenosis in a blood vessel or heart valveafter it has been treated (as by balloon angioplasty, stenting, orvalvuloplasty) with apparent success.

The treatment of a diseased site or lesion with a stent involves bothdelivery and deployment of the stent. “Delivery” refers to introducingand transporting the stent through a bodily lumen to a region, such as alesion, in a vessel that requires treatment. “Deployment” corresponds tothe expanding of the stent within the lumen at the treatment region.Delivery and deployment of a stent are accomplished by positioning thestent about one end of a catheter, inserting the end of the catheterthrough the skin into a bodily lumen, advancing the catheter in thebodily lumen to a desired treatment location, expanding the stent at thetreatment location, and removing the catheter from the lumen.

In the case of a balloon expandable stent, the stent is mounted about aballoon disposed on the catheter. Mounting the stent typically involvescompressing or crimping the stent onto the balloon. The stent is thenexpanded by inflating the balloon. The balloon may then be deflated andthe catheter withdrawn. In the case of a self-expanding stent, the stentmay be secured to the catheter via a retractable sheath or a sock. Whenthe stent is in a desired bodily location, the sheath may be withdrawnwhich allows the stent to self-expand.

The stent must be able to satisfy a number of mechanical requirements.First, the stent must be capable of withstanding the structural loads,namely radial compressive forces, imposed on the stent as it supportsthe walls of a vessel. Therefore, a stent must possess adequate radialstrength. Radial strength, which is the ability of a stent to resistradial compressive forces, is due to strength and rigidity around acircumferential direction of the stent. Radial strength and rigidity,therefore, may also be described as, hoop or circumferential strengthand rigidity.

Once expanded, the stent must adequately maintain its size and shapethroughout its service life despite the various forces that may come tobear on it, including the cyclic loading induced by the beating heart.For example, a radially directed force may tend to cause a stent torecoil inward. Generally, it is desirable to minimize recoil.

In addition, the stent must possess sufficient flexibility to allow forcrimping, expansion, and cyclic loading. Longitudinal flexibility isimportant to allow the stent to be maneuvered through a tortuousvascular path and to enable it to conform to a deployment site that maynot be linear or may be subject to flexure. Finally, the stent must bebiocompatible so as not to trigger any adverse vascular responses.

The structure of a stent is typically composed of scaffolding thatincludes a pattern or network of interconnecting structural elementsoften referred to in the art as struts or bar arms. The scaffolding canbe formed from wires, tubes, or sheets of material rolled into acylindrical shape. The scaffolding is designed so that the stent can beradially compressed (to allow crimping) and radially expanded (to allowdeployment). A conventional stent is allowed to expand and contractthrough movement of individual structural elements of a pattern withrespect to each other.

Additionally, a medicated stent may be fabricated by coating the surfaceof either a metallic or polymeric scaffolding with a polymeric carrierthat includes an active or bioactive agent or drug. Polymericscaffolding may also serve as a carrier of an active agent or drug.

After a stent is fabricated, a stent typically undergoes sterilizationto reduce the bioburden of the stent to an acceptable sterilityassurance level (SAL). There are numerous methods of sterilizing medicaldevices such as stents, the most common being ethylene oxide treatmentand treatment with ionization radiation such as electron beam and gammaradiation. Generally, it is desirable for the sterilization procedure tohave little or no adverse affects on the material properties of thestent.

SUMMARY

Various embodiments of the present invention include a method ofsterilizing a stent delivery assembly comprising: exposing a stentdelivery assembly to radiation from a radiation source, wherein acovering over a selected section of the assembly selectively modifiesthe radiation from the radiation source that is delivered to theselected section of the assembly.

Further embodiments of the present invention include a method ofsterilizing a stent delivery assembly comprising: exposing a stentdelivery assembly enclosed in a package to radiation from a radiationsource, wherein the package comprises one or more modifier sections, themodifier sections selectively modify the radiation from the radiationsource that is delivered to the selected section of the assembly.

Additional embodiments of the present invention include a system forsterilizing a stent delivery assembly with radiation, comprising: astent delivery assembly; and a package having a one or more modifiersections, the assembly being disposed within the package, wherein theone or more modifier sections are positioned relative to a selectedsection of the assembly to modify radiation delivered to the selectedsection of the assembly when radiation is directed at the assembly froma radiation source.

Other embodiments of the present invention include a system forsterilizing a stent delivery assembly with radiation, comprising: astent delivery assembly; and a covering over a selected section of theassembly, wherein the covering modifies radiation delivered to theselected section of the assembly when radiation is directed at theassembly from a radiation source.

Certain additional embodiments of the present invention include a methodof sterilizing a stent delivery assembly comprising: exposing a stentdelivery assembly to radiation from a radiation source, the assemblybeing disposed in a package supported by a fixture, wherein a modifiersection of the fixture selectively modifies the radiation from theradiation source that is delivered to a selected section of theassembly.

Some other embodiments of the present invention include a method ofsterilizing a plurality of stent delivery system assemblies with aradiation source, the method comprising: positioning a plurality ofstent catheter assemblies within packages supported on a fixture, eachof the assemblies arranged in a planar configuration in the packages;and exposing the assemblies to a radiation beam from a radiation source,the beam being at an acute angle to the planar configuration of thepackages that are positioned between the source and the fixture, whereinthe packages are arranged such that the radiation passes through morethan one of the assemblies during exposure, the delivered dose varyingwith distance between the radiation source and the fixture, one or moreof the assemblies being positioned within the packages so that aselected section of the assemblies receives a selected deliveredradiation dose.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a stent.

FIG. 2 depicts a stent delivery assembly.

FIG. 3 depicts a schematic illustration of a stent delivery assemblydisposed in a pouch.

FIG. 4A depicts a schematic illustration of a stent delivery assembly ina pouch disposed in a flat box.

FIG. 4B depicts a photograph of a pouch containing a stent deliveryassembly being disposed in a chipboard box.

FIG. 5 depicts a schematic illustration of a fixture that supports apackage.

FIG. 6A depicts the delivered dose within a material versus the depth ofpenetration of the radiation for materials of two different densities.

FIGS. 6B-D depict embodiments of modifying radiation exposure to aselection section of device.

FIG. 7A depicts a stent disposed over a distal end of a catheter.

FIG. 7B depicts a sheath disposed over stent.

FIG. 7C depicts an inner sheath 720 and an outer sheath 725 over astent.

FIG. 7D depicts a covering 730 over a distal end of a catheter.

FIG. 8A depicts a schematic illustration of a flexible package with astent delivery assembly contained therein.

FIG. 8B depicts a side view of the package of FIG. 8A.

FIG. 9A depicts a schematic illustration of a rigid package with a stentdelivery assembly contained therein.

FIG. 9B depicts a side view of the package of FIG. 9A.

FIG. 10A depicts a package with a preformed barrier portion with a stentdelivery assembly contained therein.

FIG. 10B depicts a side view of the package of FIG. 10A.

FIG. 11A depicts a package that includes a receptacle or slot forinsertion of a barrier element.

FIG. 11B depicts a side view of the package of FIG. 10A.

FIG. 12A depicts a fixture for supporting packages containing stentdelivery assemblies during sterilization.

FIG. 12B depicts a side view of the fixture of FIG. 11B supporting apackage containing a stent delivery assembly.

FIG. 13A depicts a fixture containing packages arranged in a staggeredhorizontally stacked configuration.

FIG. 13B depicts an overhead view of the fixture in FIG. 13A.

DETAILED DESCRIPTION OF THE INVENTION

Various embodiments of the present invention relate to sterilizingimplantable medical devices with radiation. In some embodiments, thedevices can be made in whole or in part of polymers. The embodimentsrelate to controlling the radiation delivered to selected sections of adevice.

The method and systems described herein may be applied generally toimplantable medical devices. The methods and systems are particularlyrelevant, for reasons discussed below, to implantable medical deviceshaving a polymeric substrate, a polymer-based coating, and/or adrug-delivery coating. A polymer-based coating may contain, for example,an active agent or drug for local administration at a diseased site. Animplantable medical device may include a polymer or non-polymersubstrate with a polymer-based coating.

Examples of implantable medical devices include self-expandable stents,balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts),artificial heart valves, cerebrospinal fluid shunts, pacemakerelectrodes, and endocardial leads (e.g., FINELINE and ENDOTAK, availablefrom Abbott Cardiovascular Systems Inc, Santa Clara, Calif.). Theunderlying structure or substrate of the device can be of virtually anydesign.

The structure of a stent in particular can have a scaffolding or asubstrate that includes a pattern of a plurality of interconnectingstructural elements or struts. FIG. 1 depicts an example of a view of astent 100. Stent 100 has a cylindrical shape and includes a pattern witha number of interconnecting structural elements or struts 110. Ingeneral, a stent pattern is designed so that the stent can be radiallycompressed (crimped) and radially expanded (to allow deployment). Thestresses involved during compression and expansion are generallydistributed throughout various structural elements of the stent pattern.The present invention is not limited to the stent pattern depicted inFIG. 1. The variation in stent patterns is virtually unlimited.

A stent such as stent 100 may be fabricated from a polymeric tube or asheet by rolling and bonding the sheet to form a tube. A stent patternmay be formed on a polymeric tube by laser cutting a pattern on thetube. Representative examples of lasers that may be used include, butare not limited to, excimer, carbon dioxide, and YAG. In otherembodiments, chemical etching may be used to form a pattern on a tube.

A stent has certain mechanical requirements that are crucial tosuccessful treatment. For example, a stent must have sufficient radialstrength to withstand structural loads, namely radial compressiveforces, imposed on the stent as it supports the walls of a vessel. Inaddition, the stent must possess sufficient flexibility to allow forcrimping, expansion, and cyclic loading. Bending elements 130, 140, and150, in particular, are subjected to a great deal of stress and strainduring use of a stent.

It is well known by those skilled in the art that the mechanicalproperties of a polymer can be modified by applying stress to a polymer.The strength and modulus of a polymer tend to be increased along thedirection of the applied stress. Therefore, in some embodiments, apolymer tube can be radially deformed prior to laser cutting to enhanceradial strength. The increase in strength and modulus can be due to theinduced molecular orientation in the circumferential direction. However,as the temperature of the polymer increases close to or above a glasstransition temperature (Tg), some or all of the induced orientation andstrength can be lost due to relaxation of polymer chains. The “glasstransition temperature,” Tg is the temperature at which the amorphousdomains of a polymer change from a brittle vitreous state to a soliddeformable or ductile state at atmospheric pressure. In other words, theTg corresponds to the temperature where the onset of segmental motion inthe chains of the polymer occurs. When an amorphous or semicrystallinepolymer is exposed to an increasing temperature, the coefficient ofexpansion and the heat capacity of the polymer both increase as thetemperature is raised, indicating increased molecular motion. As thetemperature is raised the actual molecular volume in the sample remainsconstant, and so a higher coefficient of expansion points to an increasein free volume associated with the system and therefore increasedfreedom for the molecules to move. The increasing heat capacitycorresponds to an increase in heat dissipation through movement. Tg of agiven polymer can be dependent on the heating rate and can be influencedby the thermal history of the polymer. Furthermore, the chemicalstructure of the polymer heavily influences the glass transition byaffecting mobility.

Sterilization is typically performed on medical devices, such as stents,to reduce the bioburden on the device. Bioburden refers generally to thenumber of microorganisms with which an object is contaminated. Thedegree of sterilization is typically measured by a sterility assurancelevel (SAL) which refers to the probability of a viable microorganismbeing present on a product unit after sterilization. The required SALfor a product is dependent on the intended use of the product. Forexample, a product to be used in the body's fluid path is considered aClass III device. SAL's for various medical devices can be found inmaterials from the Association for the Advancement of MedicalInstrumentation (AAMI) in Arlington, Va.

Radiation sterilization is well known to those of ordinary skill theart. Medical devices composed in whole or in part of polymers can besterilized by various kinds of radiation, including, but not limited to,electron beam (e-beam), gamma ray, ultraviolet, infra-red, ion beam,x-ray, and laser sterilization. A sterilization dose can be determinedby selecting a dose that provides a required SAL. A sample can beexposed to the required dose in one or multiple passes.

However, it is known that radiation can alter the properties of thepolymers being treated by the radiation. High-energy radiation tends toproduce ionization and excitation in polymer molecules. Theseenergy-rich species undergo dissociation, subtraction, and additionreactions in a sequence leading to chemical stability. The stabilizationprocess can occur during, immediately after, or even days, weeks, ormonths after irradiation which often results in physical and chemicalcross-linking or chain scission. Resultant physical changes can includeembrittlement, discoloration, odor generation, stiffening, andsoftening, among others.

In particular, the deterioration of the performance of polymericmaterials and drugs due to e-beam radiation sterilization has beenassociated with free radical formation in a device during radiationexposure and by reaction with other parts of the polymer chains. Thereaction is dependent on e-beam dose and level of temperature.

Additionally, exposure to radiation, such as e-beam can cause a rise intemperature of an irradiated polymer sample. The rise in temperature isdependent on the level of exposure. It has been observed that a stentdelivery assembly can increase about 7° C. per 12 kGy of radiationexposure. Mechanical properties of polymers are particularly sensitiveto changes in temperature. In particular, the effect on propertiesbecomes more profound as the temperature approaches and surpasses theglass transition temperature, Tg. It has been observed that e-beamradiation of polymer stents can result in cracking of struts duringdeployment due to onset of brittle behavior. The cracking can be due tothe increase in temperature, as well as the reduction in molecularweight. Additionally, the increase in temperature can result in a lossof some or all of the induced orientation and strength due to relaxationof polymer chains.

Furthermore, the increase in temperature can also increase the releaserate of drug resulting in a decrease of drug loading on a stent. Drugscan also degrade at increased temperatures during manufacture andstorage conditions, altering the total content and release rate of thedrug. The dose can be selected to be sufficient to sterilize the stentto a desired degree. As indicated above, the exposure can be in one ormore passes from a radiation source.

In general, a polymeric stent and balloon are more sensitive toradiation exposure than a catheter and dispenser coil. The performanceof the stent and balloon are more likely to be adversely affected by theincrease in temperature and chemical degradation caused by radiationexposure. Therefore, it is important for the delivered radiationexposure to the stent and balloon to be within a selected range. Aselected range can be, for example, 20-30 KGy or, more narrowly, 22-27KGy. On the other hand, the performance of a catheter and dispenser coilis less sensitive to radiation exposure. Thus, the catheter anddispenser coil can tolerate larger variations in delivered radiation athigher levels. In general, selected sections of a device can havedifferent desired or optimal delivered radiation range than othersections of the device.

Furthermore, in some embodiments, the stent and balloon may require alower radiation exposure for effective sterilization than the catheterand dispenser coil. The processing of a stent may result in a lowerlevel of bioburden on the stent compared to the catheter. For example, astent may be exposed to solvents such as isopropyl alcohol and acetoneduring processing. Additionally, stent material may be exposed to hightemperatures during various processing steps. Thus, the stent can have abioburden less than 5 cfu and even as low as 0-1 cfu. “CFU” is a measureof bioburden that stands for “colony-forming unit” which is a measure ofviable bacterial numbers. The required or terminal sterilization dosefor a product with 1.5 cfu is 15 KGy and a radiation dose for an 8 cfuproduct is 17.5 KGy. The delivery system may require substantiallyhigher doses than other parts of the assembly.

Therefore, for a given dose of radiation from a radiation source, it maydesirable to selectively modify the radiation delivered to a selectedsection of an implantable medical device such as a stent deliveryassembly. For example, the delivered dose to a stent can be decreased.This would reduce the degradation of the performance due to radiation.Alternatively, it may be desirable to increase a delivered dose to aselected section of a device. Some sections of the device may require ahigher dose due to high bioburden. Also, some sections may receive alower delivered dose than required due to shielding of radiation frompackaging or other portions of the device.

Stents are typically sterilized, packaged, stored, and transported in a“ready to implant” configuration in which the stent is disposed at thedistal end of a delivery system that includes a catheter and dispensercoil. FIG. 2 depicts a stent delivery assembly 200 with a stent 205disposed on a distal end of a delivery system 215. Stent 205 can becrimped over a balloon. A sheath can also be disposed over the stent tosecure the secure to the balloon. Stent delivery assembly 200 can bepackaged prior to or after radiation sterilization.

Stents and stent delivery assemblies are typically stored, transported,as well as sterilized in sealed storage containers. Such containers areadapted to protect the assembly from damage and environmental exposure(humidity, oxygen, light, etc.) which can have an adverse effect on thestent. Storage containers for a stent and delivery system can bedesigned to be any convenient form or shape that permits the effectiveenclosure of a stent and delivery system assembly contained therein. Thecontainer, however, may be compact and shaped so as to minimize storagespace occupied by the container. A container intended primarily toprotect the stent and delivery system from environmental exposure can bea pouch or sleeve. FIG. 3 depicts a schematic illustration of stentdelivery assembly 200 disposed in a pouch 230. As can be seen from FIG.3, assembly 200 is disposed or stored in a planar configuration.

In one commercially useful embodiment, a pouch can have a rectangularcross-section with a width between 8 in and 12 in and a length between10 in and 13 in. Also, depending on the types of substance(s) used toconstruct the pouch, the container can be of various degrees of rigidityor flexibility. The container can be constructed of flexible filmsrather than rigid materials because it is less likely that the sealwould be compromised by a change in atmospheric conditions duringstorage. For example, the container can be constructed of two sheets orlamina which have been joined along an edge. Also, the container can beconstructed of a single sheet or lamina which has been folded and sealedalong all edges or along all non-folded edges; or a bag or pocket whichis sealed along one or more edges. The pouches can be made from apolymer, glass, ceramic, metallic substance, or a combination thereof.Typically, the pouches are made of metallic foil.

A pouch containing a stent and delivery system can be further disposedwithin a rigid container to protect the pouch and the stent and deliverysystem contained therein. The rigid container can be, for example, abox, such as a chipboard box. FIG. 4A depicts a schematic illustrationof a stent and delivery system 200 within pouch 230 in a flat chipboardbox 240. FIG. 4B depicts a photograph of a pouch 250 containing a stentand delivery system being disposed in a chipboard box 255.

A system for sterilizing a packaged stent delivery assembly includes aradiation source, such as an e-beam source, and a fixture for supportingthe package. The support fixture is moved, for example, on a conveyerarrangement past an e-beam source in a manner that an e-beam is directedonto the stent delivery assembly. FIG. 5 depicts a schematicillustration of a fixture 500 that supports a package 505 containing astent delivery assembly (not shown). Fixture 500 includes a bottomsupport 525 and a back support arm 530. A radiation source 535 directsradiation, as shown by an arrow 540. Fixture 500 can be moved by aconveyer system (not shown) as shown by an arrow 545 past radiationsource 535 to sterilize the stent delivery assembly in package 505.

In some embodiments, the cross-section of an E-beam is circular orgenerally circular in shape, as depicted by a pulse 542 of an E-beam. Insuch embodiments, the E-beam is pulsed up and down as shown by an arrow543 to irradiate package 505 and the stent delivery assembly along anaxis from position X to position Y. Thus, as fixture 500 is conveyed inthe direction shown by arrow 545, an entire selected portion of package505 and stent delivery assembly can be irradiated. In such embodiments,the beam can pulse up and down, for example, 64 times a second.

As indicated above, the radiation delivered by a radiation source toselected sections of an implantable medical device, as shown in FIG. 5,may be greater or smaller than desired. In certain embodiments of thepresent invention, a covering over a selected section of an implantablemedical device, such as a stent delivery assembly, selectively modifiesthe radiation from the radiation source that is delivered to theselected section of the assembly. In one embodiment, the radiation canbe modified by the covering so that radiation delivered to the selectedsection is within an optimal delivered radiation range. The covering canselectively modify radiation from a radiation source so that radiationdelivered to a selected section of the assembly is higher or lower thanthe radiation delivered to the selected section without the covering.

In other embodiments, an implantable medical device can be enclosed in apackage including one or more modifier sections. The modifier sectionscan selectively modify the radiation from the radiation source that isdelivered to the selected section of the assembly In one embodiment, theradiation can be modified by the modifier sections(s) so that radiationdelivered to the selected section is within an optimal deliveredradiation range. The modifier sections can selectively modify radiationfrom a radiation source so that radiation delivered to a selectedsection of the assembly is higher or lower than the radiation deliveredto the selected section in the absence of the modifier sections.

As indicated above, radiation barriers, such as a covering and themodifier sections, can increase or decrease the radiation delivered tothe selected section. Radiation barriers can cause suchincrease/decrease through absorption, reflection (or backscattering), ora combination of thereof. The manner of modification of radiationdepends upon factors such as the thickness, density, and the reflectiveproperties of a covering or modifier section material.

Generally, the delivered dose within a material that absorbs radiationvaries with both the depth of penetration (thickness) and the density ofa material. FIG. 6A depicts the delivered dose within a radiationabsorbing material versus the depth of penetration of the radiation formaterials of two different densities, curves C1 and C2.

FIG. 6A shows that, depending on its thickness, a radiation barrierelement can increase or decrease delivered radiation or dose above orbelow the initial radiation, Di. FIG. 6A shows dose versus the density(or depth) the electrons traveled through. Di could be the radiationdose that a selected section would receive in the absence of a barrierbetween the selected section and radiation source or backscattering frommaterial on a side opposite the selected section from the radiationsource. FIG. 6A also shows that the range of increased radiationincreases to larger thicknesses as the density of the radiation barrierelement increases. Both the density and thickness of a barrier elementmaterial can be selected to obtain selected radiation delivered on aselected section. When sterilizing multiple devices sequentially orsimultaneously, in order for all of the device to receive an equalamount of dose in a selected section (e.g., all the stents the samedose) the electrons must travel through equal density by the time ithits the selected section. Various materials are known by those of skillin the art that absorb or modify radiation including various types andforms of polymers, such as foam. “Foam” can refer to a polymer foam, forexample, polystyrene foam such as Styrofoam from Dow Chemical Company,Midland, Mich.

A radiation barrier can modify or reduce radiation by reflecting orbackscattering radiation. In addition to a radiation barrier such as acovering or modifier sections of a package, radiation from the radiationsource can be backscattered to a device from, for example, from a partof a supporting fixture back (e.g., support arm 530 in FIG. 5). Metals,generally, have a tendency to reflect various kinds of radiation, suchas, electromagnetic radiation, electron beam, and ion beam radiation.Representative metals that may be used to as a reflective barriermaterial include aluminum and stainless steel.

Packaging, fixture, barriers, etc., can be designed so the radiationdoes not go through enough density to drop the dose to the selectedsection to zero. Additionally, the packaging, fixture, barriers, etc.,can be designed so that a selected section receives a minimum dose, Dm,for example, 25 kGy. Curve C1 rises from Di to Dp and then goes down toDm, and finally to zero. Thus, there is a large dose variation.

Embodiments of the present invention include selective modification ofradiation to obtain a selected delivered radiation dose at a selectedsection of a device. As described below, selective modification ofradiation can be performed using a covering, modifier section(s) inpackaging, a fixture, or a combination thereof. Three sets ofembodiments of selective modification are described herein.

In a first set of embodiments, the radiation can be selectively modifiedwith a barrier between the radiation source and the selected section.The barrier is in front of the selected section, so that the radiationfrom the radiation source passes through the barrier to the selectedsection. In such embodiments, the thickness, density of material, orboth of the barrier can be selected to obtain a selected radiation doseto the selected section.

In a second set of embodiments, a barrier in back of or on a side of theselected section opposite the incoming radiation selectively modifiesradiation. In one such embodiment, the radiation can be selectivelymodified with a barrier made from reflective material that backscattersor reflects radiation back to the selected section. The radiation passesthrough the selected section to the barrier which reflects a portion ofthe radiation back at the selected section. The total dose delivered tothe selected section is a sum of the radiation that initially passesthrough the selected section and the reflected radiation.

In an alternative embodiment of the second set of embodiments, thebarrier is made from a non-reflective material. The barrier can act as abarrier that reduces or prevents radiation backscattered from, forexample, a part of a fixture from increasing the radiation delivered tothe selected section.

In a third set of embodiments, the radiation can be selectively modifiedwith a barrier in front of and behind the selected section. Radiationpasses through the front barrier to the selected section and then isbackscattered to the selected section by the back barrier. The totaldose delivered to the selected section is a sum of the radiationmodified by the first barrier and radiation reflected from the backbarrier to the selected section. In such embodiments, the properties ofthe front barrier (thickness, density) and the reflective properties ofthe back barrier can be selected to obtain a selected deliveredradiation dose to the selected section.

FIGS. 6B-D illustrate the first set, second set, and third set ofembodiments, respectively. FIGS. 6B-D depict close-up views of across-section of a selected section 605 of an implantable medical devicewith radiation Di directed at the device as shown by an arrow 610.

FIG. 6B, which illustrates the first set of embodiments, depicts aconfiguration 601 with a radiation barrier 625. In FIG. 6B, radiationbarrier 625 can correspond to a part of a covering or modifier sectionof a package on a side of selected section 605 facing incoming radiation610 with dose, Di. Radiation 610 can be modified by barrier 625 to havedose D1, which is the radiation delivered to selected section 605.

In FIG. 6B, the radiation delivered to the selected section can beincreased above Di or decreased below Di. Barrier 625 can be a materialwith a dose curve C1 from FIG. 6A. D1 can be increased to be above Di ifthe thickness of barrier 605 is less than Ti, as shown in FIG. 6A. D1can be decreased to be below Di if the thickness is greater than Ti. Toobtain a selected delivered dose with a thinner barrier, a higherdensity material can be used. In an increases D1 to 44 kGy. Thethickness, for example, can be changed so that D1 is decreased to 30kGy. An exemplary embodiment of a barrier material can be a metal.

FIG. 6C, which illustrates the second set of embodiments, depicts aconfiguration 602 with a radiation barrier 630 behind selected section605. The radiation delivered to the selected section can be increasedabove Di. Radiation barrier 630 can correspond to a part of a covering,modifier section, or fixture on a side of selected section 605. Even ifbarrier 630 is a non-reflective material, an increase in deliveredradiation due to reflection of radiation to selected section 605 from aside opposite to selected section 605 is reduced or prevented. Ifbarrier 630 is a reflective material, a portion, D2, of radiation 610 isreflected at selected section 605. The total delivered radiation is thesum of Di and D2.

In an exemplary embodiment, Di is 25 kGy so that the initial exposure is25 kGy. A portion, D2, of the 25 kGy radiation is reflected by barrier630, for example, 5 kGy. The total delivered radiation is the sum of Diand D2, or 30 kGy.

FIG. 6D, which illustrates the third set of embodiments, depicts abarrier 615 in front of selected section 605 and a barrier 620 behindselected section 605. Radiation 610 can be modified by barrier 615 tohave dose D1. D1 can be higher or lower than Di, depending on thethickness and density of barrier 615.

If barrier 620 is a reflective material, a portion of radiation 610, D2,is reflected back at selected section 605. The total delivered radiationis the sum of D1 and D2. There are at least three possibilities with abarrier 620 being a reflective material:

(1) The total delivered radiation is above Di if barrier 615 has athickness and density such that D1 is greater than Di and D2 furtherincreases the total above Di

(2) The total delivered radiation is above Di if barrier 615 has athickness and density such that D1 is less than Di and D2 increases thetotal above Di.

(3) The total delivered radiation to selected section 605 is below Di ifbarrier 615 has a thickness and density such that Dl is less than Di andthe sum of D1 and D2 is less than Di.

If barrier 620 is a non-reflective material, the total deliveredradiation can be higher or lower than Di, depending on the thickness anddensity of barrier 615.

In an exemplary embodiment, barrier 620 is a reflective material and Diis 40, D1 is 44 kGy, and D2 is 6 kGy. The total delivered dose is 50kGy.

In some embodiments, a covering can include a sheath or a sleeve that isdisposed around a selected section of a stent delivery assembly. In suchembodiments, the selected section can include a stent with the sheath orsleeve disposed around the circumference of the stent. Additionally, theselected section can be strip of polymeric material folded over toenclose a selected section of the assembly and clipped to secure thefolded over strip.

In some embodiments, the covering for the selected section includes afirst side and a second side. The first side covers a side of theselected section facing incoming radiation and the second side covers aside of the selected section opposite the incoming radiation. The firstside can modify the radiation through absorption. The second side canmodify the radiation by backscattering of radiation at the selectedsection. Alternatively, the covering is composed of a non-reflectivematerial so that there is little modification through backscattering. Inanother embodiment, the covering covers a side of the selected sectionfacing incoming radiation with a side of the selected section oppositethe incoming radiation being free of the covering.

FIG. 7A depicts a stent 705 disposed over a distal end 700 of acatheter. FIG. 7B depicts a sheath 710 disposed over stent 705. Sheath710 can also be closed at a distal end to reduce or prevent exposure ofthe stent to bioburden. Sheath 710 can serve the dual purpose ofsecuring the stent to the catheter and as a radiation barrier. As shownby an arrow 715, radiation can be directed at distal end 700. A side 720of sheath 710 can be adapted as described above to increase or decreasethe delivered radiation to stent 705. A side 725 can also be adapted toincrease the delivered dose to stent 705 through reflection ofradiation. Sheath 710 has a thickness Ts that can be adjusted to providea desired degree of modification of radiation directed at the stent. Tscan be such that the stent receives a delivered radiation that is withina desired or optimal range.

Additionally, a material can be selected having a density that providesthe desired degree of modification. The thickness, density, and materialcan be selected so that the radiation delivered to the stent isincreased or decreased to a selected range. In another embodiment,sheath 710 can be disposed over a portion of the catheter to modify theradiation delivered to the portion.

FIG. 7C depicts an alternative embodiment of a barrier showing an innersheath 720 and an outer sheath 725. Inner sheath 720 and outer sheath725 can act together to modify the delivered radiation to the stent.Inner sheath 720 can be a sheath that is typically used to secure astent to a catheter, while outer sheath 725 can be designed to adjustthe delivered radiation to the stent. For example, a thickness Tso ofouter sheath 725 can be adjusted and the density of sheath material canbe selected to provide a desired modification of radiation. Variouscombinations of materials and thicknesses of inner and outer sheaths 720and 725 can be used to provide an optimal delivered radiation to thestent.

FIG. 7D depicts another embodiment of a covering 730 that is in the formof a half-cylinder. Covering 730 covers a side of a selected section 706of distal end 700 of a catheter 700. Covering 730, for example, can be areflective material such as metal.

Embodiments of modifier section(s) of the package can selectively modifythe radiation from a radiation source so that radiation delivered to aselected section, such as a stent, of a stent delivery assembly iswithin a selected range. In some embodiments, the modifier sections canhave radiation absorption and reflection properties different from otherportions of the package. In such embodiments, the modifier section(s)can have a different thickness, density, or be made of a differentmaterial. In one embodiment, the modifier section can be coupled to orattached to a package that otherwise has a uniform or substantiallyuniform thickness, material, and density. For example, the modifiersection can be a piece metal, foam, plastic, or other material that istaped, glued, stapled, or attached to the package. In exemplaryembodiments, a modifier section can be included in, on, or integral to apouch 200 shown in FIG. 3 or a box 240 shown in FIG. 4A.

In some embodiments, a package can have a modifier section that ispositioned on a side of the selected section facing incoming radiation.The modifier section can then modify radiation through absorption.Additionally or alternatively, a package can have a modifier sectionthat is positioned on a side of the selected section opposite to theincoming radiation. Such a modifier section can modify radiation throughreflection or backscattering of radiation at the selected section. Thethickness and density of the modifier sections can be selected to obtaina selected delivered radiation to the selected section.

FIG. 8A depicts a schematic illustration of a flexible package 800 witha stent delivery assembly 805 contained therein. A barrier element 810is attached to a section of package 800. A stent 815 of assembly 805 ispositioned behind barrier element 810. FIG. 8B depicts a side view ofpackage 800 showing barrier element 810. FIG. 8B illustrates thatpackage 800 can optionally have a barrier element 820 on its oppositeside. In an exemplary embodiment, barrier element 810 can selectivelymodify radiation directed at assembly 800 from a radiation source, asshown by arrows 825. Additionally, barrier element 820 can modifybackscattered radiation as shown by arrows 830 which is reflected, forexample, by a supporting fixture (not shown). Barrier element 830 can bereflective material that increases the radiation delivered to theselected section through reflection of radiation that passes throughbarrier 810. In an alternative embodiment, package 800 can have barrierelement 820 and be without barrier element 810.

Barrier elements 810 and 820 can be the same or different thickness,density, or material. In addition, package 800 can optionally includebarrier elements 835, 845, or both to modify delivered radiation to asection of the catheter or dispenser coil. The thickness, density, ormaterial of barrier elements 810, 820, 835, and 845 can be selected oradjusted, as discussed in reference to FIGS. 6B-D, to obtain a desiredor optimal delivered radiation exposure to stent 815 and selectedsection 840. In an alternative embodiment, barrier elements can beattached to an inner surface of package 800.

FIGS. 9A-B depicts a schematic illustration of a rigid package or box900, such as a box 230 shown in FIG. 4, with a stent delivery assembly905 contained therein. Radiation is directed at package 900 as shown byarrows 925. Backscattered radiation as shown by arrows 930 can come, forexample, from a fixture. As shown, assembly 905 is enclosed within aflexible package or pouch 903 which is contained within package 900.

FIG. 9A shows a front view of package 900 with barrier elements 910 and935 attached to package 900. Barrier element 910 is in front of a stent915 and barrier element 935 is in front of a section 940 of catheter905. FIG. 9B shows a side view of package 900. FIG. 9B shows thatpackage 900 optionally includes barrier elements 920, 945, or both on anopposite side of package 900. In an alternative embodiment, package 900can have either or both barrier elements 920 or 945 and be withoutbarrier elements 910 and 935. The thickness, density, or material ofbarrier elements 910, 920, 935, and 945 can be selected or adjusted, asdiscussed in reference to FIGS. 6B-D, to obtain a desired or optimaldelivered radiation exposure to stent 915 and section 940.

In further embodiments, the modifier sections of a package can beintegral with or incorporated with the packaging. FIG. 10A depicts apackage 1000 with a stent delivery assembly (not shown) containedtherein. Package 1000 includes a barrier portion 1005 that is integralwith, preformed, or incorporated with package 1000. FIG. 10B depicts aside view of package 1000 showing a stent delivery assembly 1015contained within package 1000. Package 1000 can optionally have abarrier portion 1010. In an alternative embodiment, package 1000 canhave barrier element 1010 and be without barrier element 1005. Stent1020 is positioned between barrier portion 1005 and a barrier portion1010, which can also be integral with, preformed, or incorporated withpackage 1000. Package 1000 can be formed of a plastic material withbarrier portions 1005 and 1010 preformed as part of package 1000.

In additional embodiments, a package can have a receptacle or sleevethat allows insertion of a barrier element. An inserted barrier elementcan selectively modify radiation delivered to a selected section of astent delivery assembly. FIG. 11A depicts a package 1100 with a stentdelivery assembly (not shown) contained therein. Package 1100 includes areceptacle or slot 1105 that is integral with or attached to package1100. Receptacle 1105 has an opening 1110 that allows insertion of abarrier element 1115 as shown by an arrow 1120. FIG. 11B depicts a sideview of package 1100 showing a stent delivery assembly 1125 containedwithin package 1100. Package 1100 can also have a receptacle 1135 for abarrier element 1140, as shown by an arrow 1145. In an alternativeembodiment, package 1100 can have receptacle 1135 with barrier element1140 and be without receptacle 1105 with barrier element 1115. Stent1130 is positioned between receptacle 1105 and a receptacle 1135, whichcan also be integral with or attached to package 1100.

Further embodiments of the present invention can include sterilizing animplantable medical device using a fixture that selectively modifies theradiation delivered to a selected section of the assembly. In suchembodiments, the fixture can be a support arm on a side opposite to thedevice that faces directed radiation. In an embodiment, the support caninclude a modifier section that selectively reflects or backscattersradiation to the selected section. For instance, the modifier sectioncan be composed of a material that is more reflective than otherportions of the support arm. In another embodiment, the modifier sectioncan selectively absorb radiation or have lower reflective propertiesthan other portions of a support arm.

FIG. 12A depicts a fixture 1200 for supporting packages containing stentdelivery assemblies during sterilization. Fixture 1200 includes a bottomsupport 1205 and a back support 1210. Back support 1210 has a modifierelement 1215. Modifier element 1215 has different radiationabsorption/reflective properties than other portions of the fixture.

FIG. 12B depicts a side view of fixture 1200 supporting a package 1220containing a stent delivery assembly 1225. Radiation is directed atpackage 1220 as shown by an arrow 1235. Stent 1230 is positioned betweenmodifier element 1215 and directed radiation 1235. If back support 1215is composed of a reflective material, a non-reflective modifier element1215 can reduce or eliminate backscatter from back support 1210 to stent1230, reducing delivered radiation to stent 1230. For example, backsupport 1215 can be composed of aluminum and modifier element 1215 canbe a non-reflective material such as foam.

Further embodiments of the present invention can include sterilizing aplurality of stent delivery assemblies disposed on a fixture. Aplurality of packages containing assemblies can be positioned on afixture. The assemblies can be arranged in a planar configuration, suchas in box 240 in FIG. 4A. An e-beam from an e-beam source can be at anacute angle to the planar configuration of the packages which arepositioned between the radiation source and the fixture. The packagesare arranged in a horizontally stacked configuration such that theradiation passes through more than one of the assemblies duringexposure. As a result, the delivered dose to the assemblies varies withdistance between the radiation source and the fixture. In suchembodiments, one or more of the assemblies can be positioned within thepackages so that a selected section of the assemblies receives aselected delivered radiation dose.

FIG. 13A depicts a fixture 1300 containing packages 1305 which arearranged in a staggered horizontally stacked configuration. Only threepackages are shown, however, it should be understood that the methoddescribed applies to more than three. The number of packages is limitedby the size of the fixture. Fixture 1300 has a bottom support 1302 and aback support 1304. Each of packages 1305 contain a stent deliveryassembly 1310 with a stent 1315 disposed at the distal end of acatheter. FIG. 13B depicts an overhead view of fixture 1300 and packages1305 along line A-A. A radiation source directs a radiation beam asshown by an arrow 1320. Radiation beam 1320 is at an acute angle θ tothe face of packages 1305. The delivered radiation to assembly 1310 ineach of packages 1305 decreases with distance along a line parallel tothe face of packages 1305, as illustrated by an arrow 1335. A selectedsection of assembly 1310, such as stent 1315, can be positioned withinone or more of packages 1305 so that the selected section has a selecteddelivered radiation. The delivered radiation to assembly 1310 or aselected section can be increased by a suitable selection of thematerial of back support 1304. If back support 1304 is composed of areflective material, the delivered radiation to assembly 1310 or aselected section can be increased. Alternatively, if back support 1304is composed of a non-reflective material, such as foam, increase ofdelivered radiation due to reflected radiation can be reduced orprevented. Additionally, a modifier section 1215 as depicted in FIGS.12A-B can be used with fixture 1300 to selectively modify deliveredradiation to a selected section.

The underlying structure or substrate of a stent can be completely or atleast in part made from a biodegradable polymer or combination ofbiodegradable polymers, a biostable polymer or combination of biostablepolymers, or a combination of biodegradable and biostable polymers.Additionally, a polymer-based coating for a surface of a device can be abiodegradable polymer or combination of biodegradable polymers, abiostable polymer or combination of biostable polymers, or a combinationof biodegradable and biostable polymers.

A polymer for use in fabricating an implantable medical device, such asa stent, can be biostable, bioabsorbable, biodegradable or bioerodable.Biostable refers to polymers that are not biodegradable. The termsbiodegradable, bioabsorbable, and bioerodable are used interchangeablyand refer to polymers that are capable of being completely degradedand/or eroded when exposed to bodily fluids such as blood and can begradually resorbed, absorbed and/or eliminated by the body. Theprocesses of breaking down and absorption of the polymer can be causedby, for example, hydrolysis and metabolic processes.

It is understood that after the process of degradation, erosion,absorption, and/or resorption has been completed, no part of the stentwill remain or in the case of coating applications on a biostablescaffolding, no polymer will remain on the device. In some embodiments,very negligible traces or residue may be left behind. For stents madefrom a biodegradable polymer, the stent is intended to remain in thebody for a duration of time until its intended function of, for example,maintaining vascular patency and/or drug delivery is accomplished.

Representative examples of polymers that may be used to fabricate asubstrate of an implantable medical device or a coating for animplantable medical device include, but are not limited to,poly(N-acetylglucosamine) (Chitin), Chitosan, poly(hydroxyvalerate),poly(lactide-co-glycolide), poly(hydroxybutyrate),poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride,poly(glycolic acid), poly(glycolide), poly(L-lactic acid),poly(L-lactide), poly(D,L-lactic acid), poly(L-lactide-co-glycolide);poly(D,L-lactide), poly(caprolactone), poly(trimethylene carbonate),polyethylene amide, polyethylene acrylate, poly(glycolicacid-co-trimethylene carbonate), co-poly(ether-esters) (e.g. PEO/PLA),polyphosphazenes, biomolecules (such as fibrin, fibrinogen, cellulose,starch, collagen and hyaluronic acid), polyurethanes, silicones,polyesters, polyolefins, polyisobutylene and ethylene-alphaolefincopolymers, acrylic polymers and copolymers other than polyacrylates,vinyl halide polymers and copolymers (such as polyvinyl chloride),polyvinyl ethers (such as polyvinyl methyl ether), polyvinylidenehalides (such as polyvinylidene chloride), polyacrylonitrile, polyvinylketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters(such as polyvinyl acetate), acrylonitrile-styrene copolymers, ABSresins, polyamides (such as Nylon 66 and polycaprolactam),polycarbonates, polyoxymethylenes, polyimides, polyethers,polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate,cellulose butyrate, cellulose acetate butyrate, cellophane, cellulosenitrate, cellulose propionate, cellulose ethers, and carboxymethylcellulose.

Additional representative examples of polymers that may be especiallywell suited for use in fabricating an implantable medical deviceaccording to the methods disclosed herein include ethylene vinyl alcoholcopolymer (commonly known by the generic name EVOH or by the trade nameEVAL), poly(butyl methacrylate), poly(vinylidenefluoride-co-hexafluororpropene) (e.g., SOLEF 21508, available fromSolvay Solexis PVDF, Thorofare, N.J.), polyvinylidene fluoride(otherwise known as KYNAR, available from ATOFINA Chemicals,Philadelphia, Pa.), ethylene-vinyl acetate copolymers, and polyethyleneglycol.

A non-polymer substrate of the device may be made of a metallic materialor an alloy such as, but not limited to, cobalt chromium alloy(ELGILOY), stainless steel (316L), high nitrogen stainless steel, e.g.,BIODUR 108, cobalt chrome alloy L-605, “MP35N,” “MP20N,” ELASTINITE(Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy,gold, magnesium, or combinations thereof. “MP35N” and “MP2ON” are tradenames for alloys of cobalt, nickel, chromium and molybdenum availablefrom Standard Press Steel Co., Jenkintown, Pa. “MP35N” consists of 35%cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consistsof 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum.

A drug or active agent can include, but is not limited to, any substancecapable of exerting a therapeutic, prophylactic, or diagnostic effect.The drugs for use in the implantable medical device, such as a stent ornon-load bearing scaffolding structure may be of any or a combination ofa therapeutic, prophylactic, or diagnostic agent. Examples of activeagents include antiproliferative substances such as actinomycin D, orderivatives and analogs thereof (manufactured by Sigma-Aldrich 1001 WestSaint Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available fromMerck). Synonyms of actinomycin D include dactinomycin, actinomycin IV,actinomycin I₁, actinomycin X₁, and actinomycin C₁. The bioactive agentcan also fall under the genus of antineoplastic, anti-inflammatory,antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic,antibiotic, antiallergic and antioxidant substances. Examples of suchantineoplastics and/or antimitotics include paclitaxel, (e.g., TAXOL® byBristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g., Taxotere®,from Aventis S. A., Frankfurt, Germany), methotrexate, azathioprine,vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g.,Adriamycin® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g.,Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples ofsuch antiplatelets, anticoagulants, antifibrin, and antithrombinsinclude aspirin, sodium heparin, low molecular weight heparins,heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin andprostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone(synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa plateletmembrane receptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax ä (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.,Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such asnifedipine), colchicine, proteins, peptides, fibroblast growth factor(FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists,lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol loweringdrug, brand name Mevacor® from Merck & Co., Inc., Whitehouse Station,N.J.), monoclonal antibodies (such as those specific forPlatelet-Derived Growth Factor (PDGF) receptors), nitroprusside,phosphodiesterase inhibitors, prostaglandin inhibitors, suramin,serotonin blockers, steroids, thioprotease inhibitors,triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example ofan antiallergic agent is permirolast potassium. Other therapeuticsubstances or agents which may be appropriate agents include cisplatin,insulin sensitizers, receptor tyrosine kinase inhibitors, carboplatin,alpha-interferon, genetically engineered epithelial cells, steroidalanti-inflammatory agents, non-steroidal anti-inflammatory agents,antivirals, anticancer drugs, anticoagulant agents, free radicalscavengers, estradiol, antibiotics, nitric oxide donors, super oxidedismutases, super oxide dismutases mimics,4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO),tacrolimus, dexamethasone, ABT-578, clobetasol, cytostatic agents,prodrugs thereof, co-drugs thereof, and a combination thereof. Othertherapeutic substances or agents may include rapamycin and structuralderivatives or functional analogs thereof, such as40-O-(2-hydroxy)ethyl-rapamycin (known by the trade name of EVEROLIMUS),40-O-(3-hydroxy)propyl-rapamycin,40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, methyl rapamycin, and40-O-tetrazole-rapamycin.

A stent storage container, for example, package 230 of FIG. 3 or package1100 of FIGS. 11A-B, can be made of various substances that form abarrier when sealed. For instance, at stent storage container can bemade of a polymer, glass, ceramic or a metallic substance such asaluminum, stainless steel or gold. If made of a metallic substance, thecontainer for example can be formed of a metallic film. Suitableexamples of films include, but are not limited to, gold, platinum,platinum/iridium alloy, tantalum, palladium, chromium, and aluminum.Suitable materials for the container may also include oxides of theabove-mentioned metals, for example, aluminum oxide. Medical storagecontainers may be obtained from, for example, Oliver Products Company ofGrand Rapids, Mich.

Suitable polymers for construction of a stent storage container caninclude polymers of polyolefins, polyurethanes, cellulosics (i.e.,polymers having mer units derived from cellulose), polyesters,polyamides, poly(hexamethylene isophthalamide/terephthalamide)(commercially available as Selar PA™), poly(ethyleneterephthalate-co-p-oxybenzoate) (PET/PHB, e.g., copolymer having about60-80 mole percent PHB), poly(hydroxy amide ethers), polyacrylates,polyacrylonitrile, acrylonitrile/styrene copolymer (commerciallyavailable as Lopac™), rubber-modified acrylonitrile/acrylate copolymer(commercially available as Barex™), liquid crystal polymers (LCP) (e.g.Vectra™ available from Hoescht-Celanese, Zenite™ available from DuPont,and Xydar™ available from Amoco Performance Chemicals), poly(phenylenesulfide), polystyrenes, polypropylenes, polycarbonates, epoxies composedof bisphenol A based diepoxides with amine cure, aliphatic polyketones(e.g., Carilon™ available from Shell, and Ketonex™ available fromBritish Petroleum), polysulfones, poly(estersulfone),poly(urethane-sulfone), poly(carbonate-sulfone), poly(3-hydroxyoxetane),poly(amino ethers), gelatin, amylose, parylene-C, parylene-D, andparylene-N.

Representative polyolefins include those based upon alpha-monoolefinmonomers having from about 2 to 6 carbon atoms and halogen substitutedolefins, i.e., halogenated polyolefins. By way of example, and notlimitation, low to high density polyethylenes, essentially unplasticizedpoly(vinyl chloride), poly(vinylidene chloride) (Saran™), poly(vinylfluoride), poly(vinylidene fluoride), poly(tetrafluoroethylene)(Teflon), poly(chlorotrifluoroethylene) (Kel-F™), and mixtures thereofare suitable. Low to high density polyethylenes are generally understoodto have densities of about 0.92 g cm⁻³ to about 0.96 g cm⁻³, however, nobright line can be drawn for density classifications and the density canvary according to the supplier.

Representative polyurethanes include polyurethanes having a glasstransition temperature above a storage or ambient temperature, forexample having a glass transition temperature of at least 40° C. to 60°C., or having a non-polar soft segment which includes a hydrocarbon,silicone, fluorosilicone, or mixtures thereof. For example, Elast-Eon™manufactured by Elastomedic/CSIRO Molecular Science, is a polyurethanewith a non-polar soft segment which is made from 1,4-butanediol,4,4′-methylenediphenyl diisocyanate, and a soft segment composed of ablend of poly(hexamethylene oxide) (PHMO) andbishydroxyethoxypropylpolydimethylsiloxane (PDMS). A useful example hasa blend of 20% by weight PHMO and 80% by weight PDMS.

Representative examples of cellulosics include, but are not limited to,cellulose acetate having a degree of substitution (DS) greater thanabout 0.8 or less than about 0.6, ethyl cellulose, cellulose nitrate,cellulose acetate butyrate, methyl cellulose, and mixtures thereof.

Representative polyesters include saturated or unsaturated polyesterssuch as, but not limited to, poly(butylene terephthalate), poly(ethylene2,6-naphthalene dicarboxylate) (PEN), and poly(ethylene terephthalate).

Representative polyamides include crystalline or amorphous polyamidessuch as, but not limited to, nylon-6, nylon-6,6, nylon-6,9, nylon-6,10,nylon-11, aromatic nylon MXD6 (manufactured by Mitsubishi Gas ChemicalAmerica, Inc.), and mixtures thereof.

Representative polyacrylates include, but are not limited to,poly(methylmethacrylate) and polymethacrylate.

A stent storage container may also be composed of copolymers of vinylmonomers with each other and olefins such as poly(ethyl vinyl acetate).

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects.

What is claimed is:
 1. A method of sterilizing a stent delivery assemblycomprising: disposing a covering over a selected section of the stentdelivery assembly; and exposing the stent delivery assembly to radiationfrom a radiation source having a delivered dose; wherein the coveringselectively modifies the radiation from the radiation source such thatthe selected section receives a modified dose of radiation, the modifieddose being less than the delivered dose and satisfying a requiredsterility assurance level (SAL).
 2. The method of claim 1, wherein theradiation is E-beam radiation.
 3. The method of claim 1, wherein thecovering absorbs radiation.
 4. The method of claim 1, wherein thecovering includes a half cylinder.
 5. The method of claim 1, wherein theselected section receives one or more doses of radiation.
 6. The methodof claim 1, wherein the covering is a folded over piece of polymermaterial.
 7. A method of sterilizing a stent delivery assemblycomprising: exposing the stent delivery assembly to a delivered dose ofradiation from a radiation source, wherein a covering over a selectedsection of the stent delivery assembly selectively modifies theradiation from the radiation source such that the selected section ofthe stent delivery assembly receives a modified dose of radiation;wherein the covering is a sheath surrounding a portion of the stentdelivery assembly; and wherein the modified dose is less than thedelivered dose and satisfies a required sterility assurance level (SAL).8. The method of claim 7, wherein the radiation is E-beam radiation. 9.The method of claim 7, wherein the selected section is a polymericstent.
 10. The method of claim 9, wherein the sheath comprises an outersheath and an inner sheath.
 11. The method of claim 10, wherein theinner sheath secures the polymeric stent to a catheter.
 12. The methodof claim 10, wherein the outer sheath has a thickness selected accordingto a dose-distribution curve to reduce the radiation delivered to thepolymeric stent.
 13. The method of claim 9, wherein the sheath includesa polymer.
 14. The method of claim 7, wherein the sheath includes afirst portion for absorbing radiation and a second portion forreflecting radiation.
 15. The method of claim 7, wherein the sheath ismade of a polymer, or a combination of metal and polymer.
 16. The methodof claim 7, wherein the sheath is disposed over a portion of a catheterto modify the radiation delivered to the portion.